Full protection from all 4 SARS-CoV-2 variants of concern in hamsters requires revision of spike antigen used for vaccination

 Sapna Sharma, Thomas Vercruysse, Lorena Sanchez-Felipe, Winnie Kerstens, Rana Abdelnabi, Caroline Foo, Viktor Lemmens, Dominique Van Looveren, Piet Maes, Guy Baele, Birgit Weynand, Philippe Lemey,  

View ORCID ProfileJohan Neyts,  View ORCID ProfileHendrik Jan Thibaut,  View ORCID ProfileKai Dallmeier

doi: https://doi.org/10.1101/2021.11.12.468374

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.11.12.468374v1.full.pdf

Abstract

Current licensed COVID-19 vaccines are based on antigen sequences of initial SARS-CoV-2 isolates that emerged in 2019. By mid 2021 these historical virus strains have been completely replaced by new cosmopolitan SARS-CoV-2 lineages. The ongoing pandemic has been further driven by emerging variants of concern (VOC) Alpha, Beta, Gamma and, lately predominant, Delta. These are characterized by an increased transmissibility and possible escape from naturally acquired or vaccine-induced immunity. We here show, using a YF17D-vectored first-generation COVID-19 vaccine (Sanchez-Felipe et al., 2021) and a stringent hamster challenge model (Abdelnabi et al., 2021) that the immunity elicited by a prototypic spike antigen is insufficient to provide optimal protection against the Beta VoC, urging for an antigenic update. We therefore designed an updated second-generation vaccine candidate that carries the sequence of a spike antigen that includes crucial epitopes from multiple VOCs. This vaccine candidate yielded a marked change in target antigen spectrum covered as demonstrated by (i) antigenic cartography and (ii) full protection against infection and virus-induced disease caused by any of the four VOCs (Alpha, Beta, Gamma and Delta) used for challenge. This more universal COVID-19 vaccine candidate also efficiently blocked direct transmission of VOC Delta from vaccinated infected hamsters to non-vaccinated sentinels under prolonged co-housing conditions. In conclusion, our data suggest that current first-generation COVID-19 vaccines need to be adapted to cover emerging sequence diversity of VOC to preserve vaccine efficacy and to contain virus spread at the community level.

Competing Interest Statement

The authors have declared no competing interest.

https://www.biorxiv.org/content/10.1101/2021.11.12.468374v1